Antioxidant activity of grapefruit seed extract on vegetable oils

The antioxidant activities of a grapefruit seed extract (GFSE) which contains tocopherols, citric acid and ascorbic acid, were investigated in vegetable oils. Different amounts of GFSE in powder were dissolved in a mixture of soybean oil–sunflower oil. The oxidation was carried out in an AOM equipment at temperatures of 98·7°C, 75°C and 66·5°C. The results indicated prooxidant effects of GFSE at 97·8°C and 75°C possibly due to a blockade effect of a hydroxyl compound by tocopherol. The inhibitor reaction orders at these temperatures were 0·902 and 0·465, respectively, while at 66·5°C the oxidation rate was inverse to GFSE concentration with reaction order of −0·420. These results seem to indicate different reaction mechanisms depending on temperature conditions. The blockade effects were explained on the basis of a proposed complex between tocopherol and citric acid molecules. © 1998 SCI.     

Electroreduction of organic compounds. 31. Electroreduction of 2- and 3-Chlorodibenzofuran in Deuterated Methanol

The cathodic reduction of dibenzofuran ( 2 ), 2-chlorodibenzofuran ( 4 ), and 3-chlorodibenzofuran ( 1 ) in deuterated methanol is investigated. The Birch-type reduction product 1,4-dibenzofuran ( 3 ) is formed from 1 via 2 , whereas 2-chloro-1,4-dihydrodibenzofuran ( 5 ) is obtained as by-product besides 3 from 4 as starting compound. Deuterium is only incorporated into the reduction products if CH₃OD or CD₃OD but not if CD₃OH are used. This observation is strongly indicative of a polar mechanism involving protonation rather than a radical mechanism with hydrogen atom abstraction to be operative.     

MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in KRAS-Mutated Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Chemotherapy, the treatment of choice in non-operable cases, achieves a dismal success rate, raising the need for new therapeutic options. In about 25% of NSCLC, the activating mutations of the KRAS oncogene define a subclass that cannot benefit from tyrosine kinase inhibitors (TKIs). The tumor suppressor miR-16 is downregulated in many human cancers, including NSCLC. The main objectives of this study were to evaluate miR-16 treatment to restore the TKI sensitivity and compare its efficacy to MEK inhibitors in KRAS-mutated NSCLC. Methods: We performed in vitro and in vivo studies to investigate whether miR-16 could be exploited to overcome TKI resistance in KRAS-mutated NSCLC. We had three goals: first, to identify the KRAS downstream effectors targeted by mir-16, second, to study the effects of miR-16 restoration on TKI resistance in KRAS-mutated NSCLC both in vitro and in vivo, and finally, to compare miR-16 and the MEK inhibitor selumetinib in reducing KRAS-mutated NSCLC growth in vitro and in vivo. Results: We demonstrated that miR-16 directly targets the three KRAS downstream effectors MAPK3, MAP2K1, and CRAF in NSCLC, restoring the sensitivity to erlotinib in KRAS-mutated NSCLC both in vitro and in vivo. We also provided evidence that the miR-16–erlotinib regimen is more effective than the selumetinib–erlotinib combination in KRAS-mutated NSCLC. Conclusions: Our findings support the biological preclinical rationale for using miR-16 in combination with erlotinib in the treatment of NSCLC with KRAS-activating mutations.     

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R₅₁₀stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G₆₆₀R) that, surprisingly, does not affect the Ca²⁺ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G₆₆₀R and R₅₁₀stop mutants and combinations with wild type TRPV6. We show that both the G₆₆₀R and R₅₁₀stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.     

Changes in Exosomal miRNA Composition in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

As much as space travel and exploration have been a goal since humankind looked up to the stars, the challenges coming with it are manifold and difficult to overcome. Therefore, researching the changes the human organism undergoes following exposure to weightlessness, on a cellular or a physiological level, is imperative to reach the goal of exploring space and new planets. Building on the results of our CellBox-1 experiment, where thyroid cancer cells were flown to the International Space Station, we are now taking advantage of the newest technological opportunities to gain more insight into the changes in cell–cell communication of these cells. Analyzing the exosomal microRNA composition after several days of microgravity might elucidate some of the proteomic changes we have reported earlier. An array scan of a total of 754 miRNA targets revealed more than 100 differentially expressed miRNAs in our samples, many of which have been implicated in thyroid disease in other studies.     

Determination of the Substitution Pattern of Cationic Starch Ethers

Degradation of cationic starches and subsequent permethylation and Hofmann-elimination of the methyl-glucosides yields the corresponding enolether derivatives, which can be analyzed by GLC and GLC-MS. The relative ratio of 2-, 3- and 6-substitution in the anhydroglucose unit as well as of un-, mono-, di- and trisubstitution in the anhydroglucose unit as well as of un-, mono-, di- and trisubstituted monomers can be determined. The experimental results are compared with the data calculated by means of a kinetic model. Only slight deviations from a random distribution in the anhydroglucose unit are observed and discussed. Enzymatic degradation of the cationic starch ethers and measurement of the liberated glucose should give indication to the distribution along the polymer chain.     

In Situ Hydroxyapatite Synthesis Enhances Biocompatibility of PVA/HA Hydrogels

Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix.     

Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

Besides serving as a structural membrane component and intermediate of the glycerolipid metabolism, lysophosphatidic acid (LPA) has a prominent role as a signaling molecule through its binding to LPA receptors at the cell surface. Extracellular LPA is primarily produced from lysophosphatidylcholine (LPC) through the activity of secreted lysophospholipase D, autotaxin (ATX). The degradation of extracellular LPA to monoacylglycerol is mediated by lipid phosphate phosphatases (LPPs) at the cell membrane. This review summarizes and interprets current literature on the role of the ATX-LPA-LPP3 axis in the regulation of energy homeostasis, insulin function, and adiposity at baseline and under conditions of obesity. We also discuss how the ATX-LPA-LPP3 axis influences obesity-related metabolic complications, including insulin resistance, fatty liver disease, and cardiomyopathy.